Neuregulins and erbB receptor expression in adult human oligodendrocytes

Deadwyler, Gail; Pouly, Sandrine; Antel, Jack P.; DeVries, George H.

doi:10.1002/1098-1136(200012)32:3<304::aid-glia90>3.0.co;2-z

Cited by 37 publications

(19 citation statements)

References 37 publications

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“…OLs use other autocrine signaling mechanisms. For example, developing OLs regulate their own survival and differentiation via the neuregulin-erbB receptor autocrine loop (45,46), and galanin was identified as an autocrine trophic signal in cytokine-treated OLs and in the cuprizone-induced demyelination model (47). The HMBG1-mediated autocrine trophic signaling evidenced in our study may harnesses neighboring OLs with a sort of self-defense system against ischemic injuries to the white matter.…”

Section: Discussionmentioning

confidence: 57%

High-mobility group box-1 as an autocrine trophic factor in white matter stroke

Choi

Cui

Chowdhury

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

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Maintenance of white matter integrity in health and disease is critical for a variety of neural functions. Ischemic stroke in the white matter frequently results in degeneration of oligodendrocytes (OLs) and myelin. Previously, we found that toll-like receptor 2 (TLR2) expressed in OLs provides cell-autonomous protective effects on ischemic OL death and demyelination in white matter stroke. Here, we identified high-mobility group box-1 (HMGB1) as an endogenous TLR2 ligand that promotes survival of OLs under ischemic stress. HMGB1 rapidly accumulated in the culture medium of OLs exposed to oxygen-glucose deprivation (OGD). This conditioned medium exhibited a protective activity against ischemic OL death that was completely abolished by immunodepletion of HMGB1. Knockdown of HMGB1 or application of glycyrrhizin, a specific HMGB1 inhibitor, aggravated OGD-induced OL death, and recombinant HMGB1 application reduced the extent of OL death in a TLR2-dependent manner. We confirmed that cytosolic translocation of HMGB1 and activation of TLR2-mediated signaling pathways occurred in a focal white matter stroke model induced by endothelin-1 injection. Animals with glycyrrhizin coinjection showed an expansion of the demyelinating lesion in a TLR2-dependent manner, accompanied by aggravation of sensorimotor behavioral deficits. These results indicate that HMGB1/ TLR2 activates an autocrine trophic signaling pathways in OLs and myelin to maintain structural and functional integrity of the white matter under ischemic conditions. white matter stroke | oligodendrocyte | toll-like receptor 2 | HMGB1 | myelination W hite matter in the vertebrate brain is characterized by the presence of myelinated axonal fibers and glial cells, predominantly myelin-producing oligodendrocytes (OLs) (1). The myelin sheath enables rapid communication of neural signals at a millisecond timescale between different parts of the cerebral cortex or different regions of the CNS (2). Therefore, maintaining the integrity of white matter in health and disease, especially of OLs and the myelin sheath, is critical to the performance of a variety of brain functions. Furthermore, recent studies have shown that myelination and OL generation in adulthood are actively regulated in response to neural activities (3, 4), highlighting the potential contribution of white matter plasticity to learning and higher cognitive functions.Ischemic stroke that occurs in the white matter often results in degeneration of OLs and demyelination (5, 6). Consequently, patients with white matter stroke suffer from a wide range of neurological dysfunctions. For example, focal ischemic stroke in the internal capsule may result in severe hemiparesis (7). Furthermore, both cognitive deficits and gait disturbance are hallmarks of Binswanger's subcortical vascular dementia that is the most severe form of white matter stroke (8). How ischemia leads to OL degeneration and demyelination is poorly understood. We previously reported that toll-like receptor 2 (TLR2) expressed in OLs plays a protect...

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Section: Discussionmentioning

confidence: 57%

High-mobility group box-1 as an autocrine trophic factor in white matter stroke

Choi

Cui

Chowdhury

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

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“…All EGFR members are present in the developing CNS, including the regions that generate oligodendrocytes (Fig. 3) and within cells spanning the oligodendrocyte lineage (Canoll et al, 1996;Pinkas-Kramarski et al, 1997;Raabe et al, 1997Raabe et al, , 2004Vartanian et al, 1997;Deadwyler et al, 2000;Flores et al, 2000;Kornblum et al, 2000;Calaora et al, 2001;Park et al, 2001;Schmucker et al, 2003). ErbB2 acts only as a heterodimer and is the preferred dimerization partner for all EGFR family members, although dimer composition is ultimately a function of both affinity and levels of expression of receptor monomers (Tzahar et al, 1996; Graus-Porta et al, 1997).…”

Section: Absence Of Erbb4 Modified Oligodendrocyte Lineage Maturationmentioning

confidence: 99%

The ErbB4 Neuregulin Receptor Mediates Suppression of Oligodendrocyte Maturation

Sussman

Vartanian

Miller

2005

Journal of Neuroscience

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Neuregulin is required for proper oligodendrocyte development, but which receptors are involved and whether neuregulin promotes or inhibits maturation remain controversial. To assess the roles of the neuregulin receptor ErbB4 in oligodendrocyte development, we examined oligodendrocyte initiation and maturation in cultures derived from erbB4 knock-out mice and rat spinal cord in the presence of neutralizing erbB4 antibodies. No differences in the development of O4 ϩ oligodendrocytes were detected in the presence or absence of erbB4 signaling. All four epidermal growth factor receptor family members were detected in the ventral neural tube at approximately the time of initial oligodendrocyte development, consistent with redundancy in neuregulin receptor signaling at the onset of oligodendrocyte development. In contrast, greater numbers of differentiated (monoclonal antibody O1 ϩ ) oligodendrocytes developed in neural tube explants from erbB4 ؊/؊ mice than either erbB4 ؉/؉ or erbB4 ؉/؊ littermates as well as in cultures treated with anti-erbB4. These data indicate that ErbB4 is not required for oligodendrocyte development and, in fact, inhibits oligodendrocyte lineage maturation. Together with previous studies, these data suggest a model in which early oligodendrocyte lineage development is regulated by promiscuous neuregulin receptor signaling, but subsequent lineage progression occurs through a balance of receptor-specific promotion or inhibition of maturation.

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“…One of these, NRG1, appears to help signal the onset of surfactant synthesis in the fetal lung (Dammann, Nielsen et al 2003) and might qualify as a brain protector in experimental ischemia (Xu, Jiang et al 2004; Xu, Ford et al 2005). We have recently suggested that NRG1 might play a role not only in adult (Deadwyler, Pouly et al 2000; Gerecke, Wyss et al 2004), but also in neonatal brain disorders (Dammann, Bueter et al 2007). …”

Section: Introductionmentioning

confidence: 99%

Neuregulin-1, the fetal endothelium, and brain damage in preterm newborns

Hoffmann

Bueter

Zscheppang

et al. 2010

Brain, Behavior, and Immunity

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Objective: To assess the potential role for Neuregulin-1 (NRG1) as a systemic endogenous protector in the setting of perinatal inflammatory brain damage. Methods:We measured NRG1-protein and mRNA levels in human umbilical venous endothelial cells (HUVECs) of different gestational ages at various durations of exposure to lipopolysaccharide (LPS). In parallel, we genotyped the donor individuals for SNP8NRG221533, a disease-related single nucleotide polymorphism in the 5′ region upstream of the NRG1 sequence. Intracellular NRG1 localization was visualized by confocal microscopy. Furthermore we analyzed the relationship between SNP8NRG221533 genotype and neurodevelopmental outcome in children born preterm. Results:We observed a positive dose-response-relationship between NRG1-mRNA and intracellular protein levels with both advancing gestational age and duration of LPS exposure in HUVECs. The presence of allele C at the SNP8NRG221533 locus was associated with an increased cellular production of NRG1 in HUVECs, and with a significantly reduced risk for cerebral palsy and developmental delay in children born preterm. Interpretation:In conclusion, our data indicate that gestational age, duration of LPS exposure, and the SNP8NRG221533 genotype affect NRG1 levels. Our results support the hypothesis that NRG1 may qualify as an endogenous protector during fetal development.

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Neuregulins and erbB receptor expression in adult human oligodendrocytes

Cited by 37 publications

References 37 publications

High-mobility group box-1 as an autocrine trophic factor in white matter stroke

High-mobility group box-1 as an autocrine trophic factor in white matter stroke

The ErbB4 Neuregulin Receptor Mediates Suppression of Oligodendrocyte Maturation

Neuregulin-1, the fetal endothelium, and brain damage in preterm newborns

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